Lysodren® therapy

What is Lysodren®?

Lysodren® (Mitotane) is an adrenal cytotoxic active substance – an antineoplastic agent which suppresses production of adrenal cortex corticosteroid hormones. 1,2

Lysodren® role in ACC

Only FDA approved treatment for inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC) 1

WARNINGS: ADRENAL CRISIS IN THE SETTING OF SHOCK OR SEVERE TRAUMA: In patients taking LYSODREN, adrenal crisis occurs in the setting of shock or severe trauma and response to shock is impaired. Administer hydrocortisone, monitor for escalating signs of shock and discontinue LYSODREN until recovery.

How Lysodren® works

Research on the mode of action of mitotane suggests two main biological effects:

  • A direct cytotoxic effect on adrenal cortical cells, mediated through mitochondrial alterations and inhibition of sterol-O-acyl transferase 1 (SOAT1) 2
  • Inhibition of corticosteroid synthesis by modifying the peripheral metabolism of cortisol and directly suppressing the production of corticosteroids from the adrenal cortex 1,4

Management of advanced ACC not amenable to radical resection

Practice Guidelines on the management of adrenocortical carcinoma in adults5

ACC: adrenocortical carcinoma: EDP: etoposide, doxorubicin, cisplatin
Adapted from Fassnacht M, et al. Eur J Endocrinol.2018;179(4):G1-G46.

Reference notes from Practice Guidelines

  1. Only in selected patients (with severe hormone excess)
  2. The following factors might guide the decision: site of disease involvement, tumor burden, symptoms, tumor grade/Ki67 index
  3. The following factors might guide the decision: site of disease involvement, tumor burden, symptoms, tumor grade/Ki67 index, and importantly kinetics of tumor growth
  4. Radiotherapy, radiofrequency ablation, cryo-ablation, microwave ablation, (chemo-) embolization
  5. Few panellists favored cisplatin + etoposide
  6. Contact specialized center

Lysodren® dosing and monitoring the therapeutic window

Lysodren® is available as 500 mg tablets.1 The total daily dose should be divided into three or four doses.1

The recommended treatment schedule is to start the patient at 2-6 g dosing per day, in three to four divided doses. Doses can then be increased incrementally to achieve a blood concentration of 14 to 20 mg/L, or as tolerated.1

Time taken to reach target levels of Lysodren® and observe clinical benefits varies from patient to patient but typically requires a minimum of 4 months of continuous treatment.6

Finding and maintaining the Lysodren® therapeutic window

Optimal Plasma Concentration Target

Mitotane Plasma Level Monitoring is to be performed on a regular and individual basis to reach/maintain an optimal therapeutic window.6

REFERENCES

1. Lysodren® prescribing information.
2. Waszut U, Szyszka P, Dworakowska D. Understanding mitotane mode of action, J Physiol Pharmacol 2017; 68 (1):13-26.
3. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma, N Engl J Med 2012; 366(23):2189-97.
4. Ghataore L, Chakraborti I, Aylwin S, et al. Effects of mitotane treatment on human steroid metabolism: implications for patient management, Endocr Connect 2012; 1(11):37-47.
5. Fassnacht M, et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4):G1-G46.
6. Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(2):273-89.

Lysodren Adverse Events1

Most Common Adverse Effects

  • Anorexia, nausea, vomiting, and diarrhea (80%)
  • Depression, dizziness, or vertigo (15%-40%)
  • Rash (15%)
  • Neutropenia
  • Hepatitis, elevation of liver enzymes
  • Growth retardation, hypothyroidism
  • Confusion, headache, ataxia, mental impairment, weakness, dysarthria
  • Maculopathy
  • Hypercholesterolemia, hypertriglyceridemia
  • Decreased blood androstenedione and decreased blood testosterone in females, increased sex hormone binding globulin in females and males, decreased blood free testosterone in males
  • Gynecomastia

Less Common Adverse Effects

  • Hypertension
  • Orthostatic hypotension, flushing
  • Generalized aching, and fever
  • Visual blurring
  • Diplopia
  • Lens opacity, retinopathy
  • Prolonged bleeding time
  • Hematuria
  • Hemorrhagic cystitis
  • Albuminuria

INDICATION AND IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING ON ADRENAL CRISIS IN THE SETTING OF SHOCK OR SEVERE TRAUMA

READ MORE ⇧
LYSODREN® is an adrenal cytotoxic agent indicated for the treatment of inoperable, functional or nonfunctional, adrenal cortical carcinoma. Warning/Adrenal crisis in the setting of shock or severe trauma: In patients taking LYSODREN®, adrenal crisis occurs in the setting of shock or severe trauma and response to shock is impaired. Administer hydrocortisone, monitor for escalating signs of shock and discontinue LYSODREN® until recovery.

CNS Toxicity: CNS toxicity, including sedation, lethargy, and vertigo, occurs with LYSODREN® treatment. Mitotane plasma concentrations exceeding 20 mcg/mL are associated with a greater incidence of toxicity.

Adrenal Insufficiency: Treatment with LYSODREN® can cause adrenal insufficiency. Institute steroid replacement as clinically indicated.

Measure free cortisol and corticotropin (ACTH) levels to achieve optimal steroid replacement.

Embryo-Fetal Toxicity: LYSODREN® can cause fetal harm when administered to a pregnant woman. Abnormal pregnancy outcomes, such as preterm births and early pregnancy loss, can occur in patients exposed to mitotane during pregnancy. Advise females of reproductive potential to use effective contraception during treatment with LYSODREN® and after discontinuation of treatment for as long as mitotane plasma levels are detectable.

Ovarian Macrocysts in Premenopausal Women: Ovarian macrocysts, often bilateral and multiple, have been reported in premenopausal patients receiving LYSODREN®. Complications from these cysts, including adnexal torsion and hemorrhagic cyst rupture, have been reported. In some cases, improvement after mitotane discontinuation has been described.

Lactation: Mitotane is excreted in human milk; however, the effect of LYSODREN® on the breastfed infant, or effect on milk production is unknown.

Because of the potential for serious adverse reactions in the breastfed infant, advise nursing women that breastfeeding is not recommended during treatment with LYSODREN® and after discontinuation of treatment for as long as mitotane plasma levels are detectable.

Hepatic Impairment: Administer LYSODREN® with caution to patients with hepatic impairment.

Common adverse reactions (≥15%) include: anorexia, nausea, vomiting and diarrhea; depression, dizziness or vertigo; and rash. LYSODREN® is a cytotoxic drug. Follow applicable special handling and disposal procedures.

Please see Full Prescribing Information, including BOXED WARNING, for LYSODREN® (mitotane) tablets.

To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Pharmacy, Inc. at 1-844-LYSODREN (1-844-597-6373) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Link to US Package Insert including Boxed Warning.

HRA Pharma Rare Diseases, 200 avenue de Paris, 92320, Chatillon, FRANCE
Tel: +33 (0) 1 40 33 94 14 / Fax: +33 (0) 1 40 33 30 87
© 2021 HRA Pharma Rare Diseases | Lysodren is a registered trademark of HRA Pharma Rare Diseases
Privacy Policy | Cookies Policy
Last updated: June 2023; LYS – US – 0016

You are now leaving Lysodren.com

Lysodren.com provides links to web sites of other organizations. A link does not constitute an endorsement of content, viewpoint, policies, products or services of that web site. Once you link to another web site not maintained by Lysodren.com, you are subject to the terms and conditions of that web site, including but not limited to its privacy policy.

You will be redirected to

Click the link above to continue or CANCEL

Lysodren